Project Summary/Abstract Permanent tooth loss is a significant health issue in the United States. Approximately 25% of adults 60 years and older have had complete tooth loss. In addition, nearly 70% of adults between the ages of 35-44 have lost at least one permanent tooth, with the number of individuals suffering from tooth loss projected to remain stable at approximately 9 million. Because of the detrimental effects associated with it, reducing tooth loss to <20% of adults over the age of 65 became a national health objective in the year 2000. Loss of permanent natural teeth negatively affects an individual?s diet and nutrition, and can substantially reduce quality of life and self-image. Tooth loss also directly impacts essential daily functions including speech and chewing due to altered or absent sensory feedback. Despite this, sensory processing of dentition remains incompletely understood, as does neural plasticity following tooth loss, despite the fact that teeth are one of the most commonly lost anatomical structures (through trauma, disease, or purposeful removal). This incomplete understanding of the neural processing that underlies tooth sensation critically impedes the development of novel strategies aimed at reducing the negative impact of tooth loss, and enhancing recovery from the lasting debilitating effects which often follow. Daily functions such as speech and chewing rely on distinguishing and combining cues from multiple sensory modalities at once in order to guide accurate perception and drive appropriate behavioral responses. The current proposal would be the first to examine: 1) how multiple sensory modalities (tactile, auditory, and visual) are integrated at the neuronal level to enhance sensory perception related to craniofacial and periodontal inputs, and 2) how multisensory neural circuits are reorganized following tooth loss. First, we will perform detailed electrophysiological mapping of periodontal and craniofacial (tactile) projections to the cerebral cortex of animal models. This cortical mapping will compare neuronal responses to tactile stimuli alone vs. responses to multisensory stimulus combinations (i.e., more than one sensory modality, such as tactile + auditory). Second, we will examine the multisensory cortical reorganization that results from tooth extraction. Altogether, these studies will provide insight into: 1) the neural physiology underlying dental and craniofacial sensory perception, 2) the role that additional sensory modalities play in dental and craniofacial sensation, and 3) the neural plasticity caused by the loss of normal sensory inputs from the teeth that affects those suffering from permanent tooth loss. These fundamental advances in the understanding of tooth sensation are essential for driving future data-driven, novel therapeutic strategies aimed at reducing the negative impact of tooth loss, and enhancing recovery from tooth loss, ultimately improving dental, oral, and craniofacial health in a large proportion of the U.S. population.